Background : The associations of vascular risk factors (VRFs) , apolipoprotein E (APOE) ɛ4 allele, and translocase of outer mitochondrial membrane 40 (TOMM40) G allele with cognitive function have been investigated mostly in western societies. In the present study, we sought to examine the associations of VRFs, APOE ε4 allele, and TMM40 G allele (rs2075650) with global cognitive function among Chinese older adults, with a focus on potential interactions between VRFs and the susceptibility genes. Methods : This is a cross-sectional study that included 422 participants (mean age 69.2 years, 54.3% female) in the China Longitudinal Ageing Study , who were free of dementia. Data were collected through interviews, clinical examinations, and laboratory tests. The clustering of multiple VRFs was scored by counting the number of VRFs potentially related to cognitive function. Global cognitive function was assessed with the Mini-Mental State Examination (MMSE). Data were analyzed with multiple general linear regression models. Results : Physical inactivity and diabetes were independently associated with performance lower MMSE score ( p <0.05). Moreover, physical inactivity interacted with APOE ε4 and TOMM40 G allele (rs2075650), and diabetes interacted with TOM40 G allele to affect cognitive function, such that having physical inactivity in combination with either APOE ε4 allele or TOMM40 G allele, or having diabetes and TOMM40 G allele, compared to having neither, was significantly associated with markedly lower MMSE scores ( p <0.05). Finally, when four modifiable VRFs (i.e., current smoking, physical inactivity, high LDL-C, and diabetes) were aggregated, an increasing number of having these factors was associated with a decreasing MMSE score in a dose-response manner ( p for trend<0.05). Conclusion : Some VRFs (e.g., physical inactivity and diabetes), when concurrently occurring with APOE ε4 or TOMM40 G allele, are associated with substantially poor performance in global cognitive function among the Chinese elderly .